Despite rapid urbanization and environmental changes in most areas of sub-Saharan Africa, Plasmodium transmission and malaria disease in urban settings remains pooriy understood. Limited epidemiological evidence of urban disease and vector abundance suggests considerable heterogeneity, as incidence appears to be increasing. This study will investigate diverse ecological, social, and behavioral determinants of malaria risk in and around urban areas of Blantyre, Malawi to better understand household-scale drivers of transmission and disease. Standard epidemiological methods, combined with new tools involving satellite images, space-time statistics and molecular diagnosis will address four Aims. Under Aim 1, we will characterize variation in malaria incidence throughout Malawi and determine associations with specific environmental characteristics using existing passive surveillance of cases (2002-2015) and three rounds of DHS active surveillance. Aim 2 involves a multi-year, health-facility-based, case-control study of Plasmodium infection and malaria in 6 s 59 month-old children from households in diverse social and ecological environments and levels of urbanicity. The importance of assets and behaviors, including travel, as they affect variation in transmission in/around housholds will be explored through questionnaires that accompany observations of household conditions. Studies under Aim 3 will expand on this work during two years by characterizing SNP-based genotypes of Plasmodium from people and mosquitoes in different urban and rural habitats to further explore transmission locations. Time series analyses in Aim 4 will address space-time variability and risk of environmentally-promoted epidemics. Social, economic and ecologic characteristics of housholds will be evaluated to better contextualize the urban-rural continuum. Together, we seek to better understand the complex interplay of multiple drivers of malaria risk across the spectrum of conditions represented by this urban-rural continuum, and determine which are most amenable to intervention. Ultimately, these studies should help to inform prevention policy and efficient delivery of interventions to those in greatest need.